T-Helper 2 and 3 type immunity to trophoblast in successful in vitro fertilization-embryo transfer

Abstract

To determine whether peripheral blood mononuclear cell (PBMC) secretion of T-helper (Th)-1 type cytokines and Th-2 and Th-3 type cytokines in women undergoing in vitro fertilization-embryo transfer (IVF-ET) is associated with therapeutic failure and success, respectively. Cohort study. Academic medical center. One hundred one women undergoing IVF-ET and 19 fertile controls. Peripheral blood was obtained from women undergoing IVF-ET before oocyte retrieval and from 19 nonpregnant fertile controls. The PBMCs were cultured in the presence or absence of a protein extract from either a trophoblast cell line or sperm membrane. Supernatants from PBMC cultures were tested by enzyme-linked immunoabsorbent assay (ELISA) for the Th-1 type cytokines tumor necrosis factor-alpha (TNF)-alpha) and interferon-gamma (IFN)-gamma), the Th-2 type cytokines interleukin (IL)-6 and IL-10, and the Th-3 type cytokine transforming growth factor (TGF)-beta1. Levels of IL-6 and IL-10 were significantly higher in controls than in infertile women with endometriosis, and levels of IL-10 were higher in controls than in women with unexplained infertility. No differences were found in unstimulated levels of TNF-alpha, IFN-gamma, or TGF-beta1 between infertile patients and controls. In trophoblast-stimulated PBMC cultures, levels of TGF-beta1 were significantly lower in subjects who experienced failed compared with ongoing pregnancies. Baseline PBMC secretion of IL-6 and IL-10 is higher in fertile controls than in women with endometriosis, and IL-10 secretion is also higher than in women with unexplained infertility. Trophoblast-stimulated PBMC secretion of TGF-beta1 is positively associated with the establishment of successful pregnancy in women undergoing IVF-ET. Our study provides novel evidence to support a faciliatory role of Th-2 and Th-3 type responses to trophoblast in early pregnancy.